UroEDIC Bladder: Bladder Dysfunction in Type 1 Diabetes

UroEDIC 膀胱：1 型糖尿病的膀胱功能障碍

基本信息

批准号：
10606540
负责人：
ARUNA V SARMA
金额：
$ 61.94万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10606540
关键词：
Achievement Afferent Neurons Amputation Ancillary Study Autonomic Dysfunction Bladder Bladder Dysfunction Blindness Cells Cessation of life Clinical Clinical Data Complications of Diabetes Mellitus Data Detection Diabetes Mellitus Disease Disease remission Epidemiology Epithelium Esthesia Evaluation Face Frequencies Functional disorder Funding Future Gender Gene Expression Profile Gene Expression Profiling Genetic Transcription Glycosylated hemoglobin A Goals High Prevalence Human Hyperglycemia Impaired cognition Insulin Insulin-Dependent Diabetes Mellitus Intervention Knowledge Laboratories Link Machine Learning Measurement Measures Medical Mental Depression Metabolic Modeling Molecular National Institute of Diabetes and Digestive and Kidney Diseases Natural History Overactive Bladder Participant Pathogenesis Pathway interactions Patients Pattern Persons Phenotype Play Population Prevention Publications Publishing Quality of life Research Research Personnel Residual state Risk Risk Factors Running Severities Signal Transduction Specimen Symptoms Systems Biology Techniques Testing Time United States National Institutes of Health Urinary Incontinence Urine Urologic Diseases Urology Urothelium Variant Woman Work autonomic neuropathy case control cohort design diabetes control diabetic experience follow-up glycemic control incontinence symptom insight lower urinary tract symptoms mechanotransduction member men multidisciplinary novel predictive modeling randomized trial transcriptome sequencing transmission process treatment strategy trial enrollment urinary urologic

项目摘要

PROJECT SUMMARY The Diabetes Control and Complication Trial (DCCT) and its observational follow up Epidemiology of Diabetes Intervention and Complications (EDIC) represent landmark achievements in diabetes research. The DCCT enrolled 1441 men and women with type 1 diabetes (T1D) in a randomized trial of intensive vs. conventional insulin therapy, delaying the onset and progression of diabetic complications and dramatically changing the management of patients worldwide. Implementation of tight glycemic control has reduced the frequency of devastating complications of T1D such as early death, blindness and amputation. Women and men with T1D face new challenges including cognitive decline, autonomic dysfunction and urological disorders. UroEDIC, an ancillary study examining urological complications in the DCCT/EDIC cohort, combines over 25 years of detailed medical information and >90% participation in urological symptom assessment annually since 2010, making it the longest running most extensive urological evaluation of persons with T1D. The previous funding cycle identified lower urinary tract symptoms (LUTS) and urinary incontinence (UI) as urological disorders in men and women with T1D with the highest prevalence and greatest impact on quality of life (QOL). By linking powerful longitudinal urological phenotypes with extensive clinical and laboratory data of the DCCT/EDIC, we can substantially deepen our understanding of diabetes associated urinary complications. Preliminary analyses show that although many patients develop a fixed state of LUTS or UI, many others move in and out of the state over time. Our overall hypothesis is that metabolic, autonomic and epithelial dysfunctions are associated with persistent and reversible subphenotypes of LUTS and UI in men and women with diabetes. Observations also indicate bladder overactivity in both genders is increasing in this cohort. However, there is a lack of understanding of the burden and impact of other diabetic bladder problems, particularly diabetic cystopathy, classically described as decreased bladder sensation, poor contractility and high residual urine volume. The goals of UroEDIC Bladder, therefore, are to 1) characterize the full spectrum of bladder dysfunction in T1D, 2) create risk models that explain the progression and remission of LUTS/UI, and 3) identify mechanistic themes underpinning the persistence of these symptoms. The specific aims of this project are designed to incorporate newly proposed and available longitudinal data on bladder retention, autonomic dysfunction and novel transcriptional signatures with the full range of DCCT/EDIC measurements to gain deeper insight into the longitudinal patterns and mechanisms of LUTS/UI and comprehensively characterize diabetic bladder dysfunction in T1D.

项目摘要糖尿病控制和并发症试验（DCCT）及其观察性随访糖尿病的流行病学干预和并发症（EDIC）代表糖尿病研究中的具有里程碑意义的成就。 DCCT 在一项强化与常规的随机试验中，招募了1441名患有1型糖尿病（T1D）的男性和女性胰岛素治疗，延迟糖尿病并发症的发作和进展，并大大改变全球患者的管理。紧密血糖控制的实施降低了 T1D的毁灭性并发症，例如早期死亡，失明和截肢。男性和男士与T1D 面临新的挑战，包括认知能力下降，自主神经功能障碍和泌尿科疾病。 Uroedic，一个辅助研究研究了DCCT/EDIC队列中的泌尿外识并发症，结合了25年以上每年详细的医疗信息和> 90％的参与泌尿外科症状评估自2010年以来，它是对T1D患者的最广泛泌尿外科评估。以前的资金周期确定较低的尿路症状（LUTS）和尿失禁（UI）为患有T1D的男性和女性的泌尿科障碍，患病率最高，对质量的影响最大生活（QoL）。通过将强大的纵向泌尿外科表型与广泛的临床和实验室数据联系起来 DCCT/EDIC，我们可以大大加深对糖尿病相关的尿液并发症的理解。初步分析表明，尽管许多患者会发展出固定的LUTS或UI状态，但许多其他患者移动随着时间的流逝，进出州。我们的总体假设是代谢，自主和上皮功能障碍与男性和女人的LUTS和UI的持续和可逆亚表征有关糖尿病。观察结果还表明，在该队列中，两种性别的膀胱过度活动都在增加。但是，缺乏对其他糖尿病膀胱问题的负担和影响的了解，特别是糖尿病性膀胱病，经典地描述为膀胱感觉降低，收缩性差和高残余尿量。因此，Uroedic膀胱的目标是1）表征整个光谱 T1D中的膀胱功能障碍，2）创建风险模型，以解释LUTS/UI的进展和缓解， 3）确定基于这些症状持久性的机械主题。具体目的该项目旨在合并新提出的膀胱和可用纵向数据保留，自主功能障碍和新颖的转录特征全部 DCCT/EDIC测量值，以更深入地了解纵向模式和机制 LUTS/UI和全面表征T1D中的糖尿病性膀胱功能障碍。